Análisis de la interacción de E6-prototipo de VPH-16 y sus variantes E6-AAa y E6-AAc con MAGI 1 y el efecto en su degradación.

Abstract

Oncogenic protein E6 from Human Papilloma Virus 16 (HPV-16) 18 mediates the degradation of Membrane-associated guanylate kinase with inverted 19 domain structure-1 (MAGI-1), throughout the interaction of its protein binding motif 20 (PBM) with the Discs-large homologous regions 1 (PDZ1) domain of MAG1-1. 21 Generic variation in the E6 gene that translates to changes in the protein¿s amino 22 acidic sequence modifies the interaction of E6 with the cellular protein MAGI-1. 23 MAGI-1 is a scaffolding protein found at tight junctions of epithelial cells, where it 24 interacts with a variety of proteins regulating signaling pathways. MAGI-1 is a 25 multidomain protein containing two WW (rsp-domain-9), one guanylate kinase-like, 26 and six PDZ domains. PDZ domains played an important role in the function of 27 MAGI-1 and served as targets for several viral proteins including the HPV-16 E6. 28 The aim of this work was to evaluate, with an in silico approach, employing molecular 29 dynamics simulation and protein-protein docking, the interaction of the intragenic 30 variants E-G350 (L83V), E-C188/G350 (E29Q/L83V), E-A176/G350 (D25N/L83V), 31 E6-AAa (Q14H/H78Y/83V) y E6-AAc (Q14H/I27RH78Y/L83V) and E6-reference of 32 HPV-16 with MAGI-1. We found that variants E-G350, E-C188/G350, E-A176/G350, 33 AAa and AAc increase their affinity to our two models of MAGI-1 compared to 34 E6-reference.